Research in our laboratory is directed toward the characterization and quantitation of lipoprotein-cell interactions and its impact on cellular cholesterol and cholesteryl ester metabolism. We have recently developed methods for quantitating and analyzing freely reversible lipoprotein binding to intact cells as well as isolated membrane from several sources. Using these techniques, insights have been made on the role of the low density lipoprotein receptor on cholesterol transport and its importance in modulating intracellular enzymes crucial to cholesterol and cholesteryl ester metabolism. 3-hydroxy-3-methylglutaryl coenzyme A reductase, acid ester hydrolase and neutral ester hydrolase studies conducted on tissues from patients homozygous for familial hypercholesterolemia suggest that the receptor defect for low density lipoproteins results in enhanced hepatic biosynthesis of low density lipoproteins. Previous studies on intracellular cholesterol metabolism in Wolman's disease and Cholesteryl Ester Storage Disease have been extended and the studies on niacin and neomycin as hypocholesterolemic agents in patients with type II lipoprotein phenotypes and the value of niacin in lipoprotein phenotypes III and V continue.